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NY-ESO-1與MAGE-As家族在人乳腺癌組織中的表達(dá)及與腫瘤浸潤(rùn)性T細(xì)胞的相關(guān)性研究

發(fā)布時(shí)間:2018-09-13 15:03
【摘要】:目的:探討人黑色素瘤抗原(melanoma antigen gene-As,MAGE-As)、食管鱗狀細(xì)胞癌抗原(New York-esop Hageal-1,NY-ESO-1)在乳腺癌中的表達(dá)情況及意義;同時(shí)探討在四種分子亞型的乳腺癌中NY-ESO-1、MAGE-As的表達(dá)差異及與細(xì)胞毒性T淋巴細(xì)胞(cytotoxic T lymphocytes,CTL)的相關(guān)性。方法:1.收集從2014年1月—2016年1月至本院住院且最終在組織病理學(xué)上確診是浸潤(rùn)性乳腺癌的組織標(biāo)本150例,同時(shí)在已選定的乳腺癌組織標(biāo)本中用隨機(jī)數(shù)法選擇50例距癌組織5cm外病理確診為正常乳腺組織的標(biāo)本。2.整理歸納入組樣本對(duì)應(yīng)病人的一般信息資料如:患者的年齡、腫瘤的病理大小、淋巴結(jié)狀態(tài)、pTNM分期、脈管浸潤(rùn)癌栓、WHO分級(jí)等。3.根據(jù)2013年St.Gellen對(duì)乳腺癌的分型標(biāo)準(zhǔn),將入選樣本分為L(zhǎng)uminal A、B型,HER-2亞型及三陰型。4.利用Envision法檢測(cè)選取的標(biāo)本組織中NY-ESO-1、MAGE-As的表達(dá)及癌組織中CTL的浸潤(rùn)情況。5.對(duì)不同分子分型的乳腺癌NY-ESO-1、MAGE-As的表達(dá)進(jìn)行分析并與CTL的浸潤(rùn)情況進(jìn)行相關(guān)性分析。結(jié)果:1.NY-ESO-1、MAGE-As在正常乳腺組織中不表達(dá),NY-ESO-1在乳腺癌中的表達(dá)率為8.7%(13/150),NY-ESO-1在兩種不同組織中表達(dá)具有差異性(χ2=3.32 P=0.021);MAGE-As在乳腺癌中的陽性率為38.7%(58/150),與正常組織中的陽性率相較,MAGE-As在乳腺癌組織中表達(dá)較高(χ2=27.23 P=0.000);NY-ESO-1、MAGE-As在乳腺癌組織中的表達(dá)無顯著相關(guān)(r=0.047 P=0.565)。2.NY-ESO-1在乳腺癌中的表達(dá)僅與組織學(xué)分級(jí)有關(guān)(χ2=16.66P=0.000),與年齡(χ2=0.025 P=0.426)、腫瘤大小(χ2=1.353 P=0.245)、淋巴結(jié)轉(zhuǎn)移(χ2=0.604 P=0.739)、脈管瘤栓(χ2=1.001 P=0.159)、病理分期(χ2=0.027 P=0.870)無顯著相關(guān)(P0.05);MAGR-As表達(dá)與脈管瘤栓(χ2=0.695 P=0.278)、組織學(xué)分級(jí)(χ2=4.243 P=0.120)、年齡(χ2=2.1 P=0.102)、腫瘤大小(χ2=1.875 P=0.171)、淋巴結(jié)轉(zhuǎn)移(χ2=1.060 P=0.589)、病理分期(χ2=6.857 P=0.077)、ER狀態(tài)(χ2=2.513 P=0.131)、PR狀態(tài)(χ2=1.949 P=0.163)均無相關(guān)性(P0.05)。3.NY-ESO-1的表達(dá)與乳腺癌的不同分子分型有關(guān)(χ2=42.389P=0.000),且僅表達(dá)在三陰型乳腺癌中(P0.05);MAGE-As在不同分子分型中表達(dá)具有差異性(χ2=7.925 P=0.048);CTL在乳腺癌組織中的浸潤(rùn)程度在四種分子亞型中未表現(xiàn)出差異性(χ2=8.990P=0.438);4.NY-ESO-1的表達(dá)與乳腺癌中CTL不同浸潤(rùn)程度有關(guān)(χ2=8.917P=0.03),且在三陰型乳腺癌中NY-ESO-1的表達(dá)與較高水平的CTL具有顯著的相關(guān)性(χ2=5.593 P=0.018);MAGE-As的表達(dá)與乳腺癌中CTL不同浸潤(rùn)程度無關(guān)(χ2=1.138 P=0.286),但MAGE-As在HER-2亞型乳腺癌中與CTL不同浸潤(rùn)程度的有關(guān)(χ2=5.818 P=0.016),與Luminal A型乳腺癌(χ2=1.855 P=0.173)、Luminal B型(χ2=1.678P=0.195)、三陰型乳腺癌(χ2=1.779 P=0.180)中CTL浸潤(rùn)程度均無關(guān)(P0.05)。結(jié)論:1.NY-ESO-1、MAGE-As抗原蛋白在乳腺癌中高表達(dá),是乳腺癌的相關(guān)性抗原。2、NY-ESO-1僅在不同WHO分級(jí)中表現(xiàn)出差異,與年齡、腫瘤大小、淋巴結(jié)狀態(tài)、脈管瘤栓、pTNM分期無關(guān);MAGR-As表達(dá)與WHO分級(jí)、年齡、腫瘤大小、淋巴結(jié)狀態(tài)、pTNM分期、脈管瘤栓均無關(guān)。3、NY-ESO-1在TNBC中特異性表達(dá),并且其表達(dá)與CTL的浸潤(rùn)程度成正相關(guān);MAGE-As表達(dá)與乳腺癌的不同分子亞型有關(guān),并且MAGE-As僅在HER-2亞型乳腺癌中與CTL浸潤(rùn)程度呈負(fù)相關(guān)。
[Abstract]:Objective: To investigate the expression and significance of human melanoma antigen gene-As (MAGE-As) and esophageal squamous cell carcinoma antigen (NY-ESO-1) in breast cancer, and to explore the difference between the expression of NY-ESO-1 and MAGE-As and cytotoxic T lymphocyte (cytotoxic T lymphocyte) in four molecular subtypes of breast cancer. Methods: 1. 150 specimens of invasive breast cancer were collected from January 2014 to January 2016, and 50 specimens of normal breast tissue were selected by random number method. 2. According to the classification standard of breast cancer by St. Gellen in 2013, the selected samples were divided into Luminal A, B, HER-2 subtypes and three negative subtypes. The expression of NY-ESO-1, MAGE-As and the infiltration of CTL in breast cancer tissues were studied. 5. The expression of NY-ESO-1 and MAGE-As in different molecular types of breast cancer was analyzed and correlated with the infiltration of CTL. Results: 1. NY-ESO-1, MAGE-As were not expressed in normal breast tissues, and the expression of NY-ESO-1 in breast cancer was 8.7% (13/15). The positive rate of MAGE-As in breast cancer was 38.7% (58/150), which was higher than that in normal tissues (_2 = 27.23 P = 0.000); the expression of NY-ESO-1 and MAGE-As in breast cancer was not significantly correlated (r = 0.047 P = 0.56 P = 0.000). The expression of NY-ESO-1 in breast cancer was only correlated with histological grade (962 = 16.66P = 0.000), age (962 = 0.025 P = 0.426), tumor size (\962 = 1.353 P = 0.245), lymph node metasta (\962 = 0.604 P = 0.604 P = 0.739), angioma embolism (\962 = 1.001 P = 1.001 P = 0.159), pathologstage (\\962 = 0.027 = 0.027 = 0.877 = 0.87P = 0.876), tumor size (962 = 1.35 = 1.35 = 1.353 P = 1.35 = 0.35 = 0.Expression of-As and Vascular Tumor Thrombus (_2=0) 695 P = 0.278, histological grade (962 = 4.243 P = 0.077), age (962 = 2.1 P = 0.120), age (962 = 2.1 P = 0.102), tumor size (962 = 1.875 P = 0.171), lymph node metasta (962 = 1.060 P = 0.0 P = 0.589), pathologstag (962 = 6.857 P = 0.77 = 0.077), ER status (\\\\\\\\\\2 = 2.3 P = 0.131 = 0.1), PRstate (\\\\\Correlation (P 0.05). 3. Expression of NY-ESO-1 and Different Molecular Fractions of Breast Cancer The expression of MAGE-As was different in different molecular types (2 = 7.925 P = 0.048); the infiltration degree of CTL in breast cancer tissue showed no difference among the four molecular subtypes (2 = 8.990 P = 0.438); the expression of 4.NY-ESO-1 was different from that of CTL in breast cancer tissue. The expression of NY-ESO-1 in triple-negative breast cancer was significantly correlated with the higher level of CTL (_2 = 5.593 P = 0.018); the expression of MAGE-As was not correlated with the different degree of invasion of CTL in breast cancer (_2 = 1.138 P = 0.286), but MAGE-As was correlated with the different degree of invasion of CTL in HER-2 subtype breast cancer (_2 = 5.818 P = 0.018). Conclusion: 1. NY-ESO-1, MAGE-As antigen protein is highly expressed in breast cancer, and it is associated with breast cancer antigen. 2. NY-ESO-1 is only different in different WHO grades. The expression of MAGR-As was not correlated with WHO grade, age, tumor size, lymph node status, pTNM stage, and vascular thrombus. 3. The expression of NY-ESO-1 in TNBC was positively correlated with the infiltration of CTL. The expression of MAGE-As was positively correlated with different molecular subtypes of breast cancer. Guan, and MAGE-As only negatively correlated with CTL infiltration in HER-2 subtype breast cancer.
【學(xué)位授予單位】:西南醫(yī)科大學(xué)
【學(xué)位級(jí)別】:碩士
【學(xué)位授予年份】:2017
【分類號(hào)】:R737.9

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